Viral infections are believed to play an etiologic role in multiple disorders which affect the inner ear. Cytomegalovirus, in particular, is one virus which is recognized as being the most important infectious cause of sensorineural hearing loss in the U.S. While viruses are implicated in these disorders, little is actually known about the pathogenesis of inner ear viral infections. We have developed a reproducible guinea pig model of cytomegalovirus labyrinthitis, in which non-immune animals become deaf and immune animals maintain their hearing upon subsequent inner ear viral challenge. Through an interdisciplinary approach in which the immunologic, virologic, electrophysiologic, morphologic and metabolic aspects of this disease will be investigated, the following basic questions regarding this disorder will be addressed: 1) What are the specific characteristics of GPCMV labyrinthitis? 2) What are the local inner ear and systemic immune responses to GPCMV labyrinthitis? 3) What are the physiological and biochemical effects of GPCMV labyrinthitis? 4) What therapeutic measures can avert viral injury in the inner ear? Through the use of immunoassay, immunohistochemical localization studies at the light and electron microscopic level, adoptive transfer experiments, electro-physiological monitoring, and cochlear and CNS 2-deoxyglucose and energy dispersive x-ray analysis studies, a better understanding of the basic mechanisms involved in the pathogenesis of viral inner ear infections should emerge.